Exercise protects against cancer – but how?

People who regularly exercise have a lower risk of developing at least 13 different cancer types; and in those who do get cancer, exercise is associated with a reduced risk of mortality and disease recurrence. This reduced risk has mainly been linked to chronic adaptations to exercise training i.e. the lowering of resting levels of common cancer risk factors such as sex hormones, insulin and pro-inflammatory cytokines.

But more recently, a study found that blood (serum) collected after a single bout of exercise (‘acute exercise’) was able to reduce cancer cell growth. Interestingly, serum collected at rest but after six months of exercise training had no effect. This suggests that the biochemical changes involved in the acute response to exercise can have direct anti-cancer effects. And it may be the cumulative effect of these repetitive increases in acute factors driving the benefits of regular exercise.

Let’s take a look at some of the potential mechanisms underlying the protective effect of every exercise bout.

Myokines

As we exercise, our muscles contract and release hundreds of tiny proteins called myokines. Some of these myokines have been shown to directly inhibit cancer cell growth. For example, Irisin and Oncostatin M reduced breast cancer cell viability in vitro, while SPARC was found to reduce colon tumor formation in mice. These anti-growth effects have been linked to the ability of myokines to act as antagonists for the Wnt/β-catenin signalling pathway.

More indirectly, myokines can regulate anti-tumor immune cells e.g. natural killer (NK) and T cells. For example, exercise-induced increases in the myokine IL-6 was shown to increase NK cell redistribution, and ultimately reduce tumor growth.

Stress hormones

Figure is taken from Dethlefsen et al. (2017).

Exercise is a stressor to the body, which at high intensity can lead to the release of stress hormones i.e. epinephrine (adrenaline) and norepinephrine (noradrenaline), from our adrenal glands. These catecholamines have been shown to directly inhibit breast cancer cell growth in vitro, as well as tumor growth in vivo, which may be through regulation of the Hippo signalling pathway.

The release of these acute ‘exercise factors’ into circulation is dependent on the intensity, duration and mode of exercise. And although the increases can be large, they are short-lasting. This suggests that the frequency of exercise is likely to be key when designing exercise interventions to target cancer cell growth.

The bottom line

Repetitive acute changes in our serum profile (e.g. increases in catecholamines and myokines) are potential mechanisms linking exercise to cancer protection. But there are lots of other proteins, hormones, metabolites altered by acute exercise which could also be contributing – research in this area is very much in its early stages! Importantly, this understanding will help us to determine the optimal exercise prescription (frequency, intensity, duration and type of exercise) for the prevention and treatment of cancer.

Further reading:

Hojman, P., Gehl, J., Christensen, J. F., & Pedersen, B. K. (2018). Molecular mechanisms linking exercise to cancer prevention and treatment. Cell Metabolism27 (1), 10-21. DOI: 10.1016/j.cmet.2017.09.015

Dethlefsen, C., Pedersen, K. S., & Hojman, P. (2017). Every exercise bout matters: linking systemic exercise responses to breast cancer control. Breast Cancer Research and Treatment162 (3), 399-408. DOI: 10.1007/s10549-017-4129-4

About the author:

Rachael Kemp is a PhD student in Sports Science at Swansea University. Find her on ResearchGate and Twitter to stay up to date with future exercise and cancer cell research.

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